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H Schmidt

Publications and source records attributed to H Schmidt.

At least 523 records · Page 29Linked to original sources
PubMed1994

AML: immunophenotypic heterogeneity and prognostic significance of c-kit expression.

Antigenic profiles in AML that have generally accepted prognostic significance, and allow treatment stratification, have not yet been defined. In a previous report of Ashman et al., the proto-oncogene c-kit defined by binding of the moab YB5.B8 was expressed on about one third of AML cases, mainly of the undifferentiated FAB-subtypes and associated with poor prognosis and overall survival. In this study, the moab 17F11 also directed against the c-kit structure stained 41/47 AML and 6/8 CML blast specimens, whereas all investigated 40 ALL samples were c-kit negative. c-kit was not restricted to any particular, undifferentiated FAB-subtype, but found in 9/9 AML-M0/M1, 18/19 AML-M2, 0/1 AML-M3, 11/13 AML-M4 and 3/5 AML-M5 subtypes. Immunophenotypical analysis showed no restriction of c-kit expression to immature, CD34+ precursors, but c-kit was also expressed on CD4+ CD34- precursor cells differentiating towards the monocyte lineage. In addition, multi-color labelings revealed an extraordinary heterogeneity of concomitant antigen expression on c-kit+ cells 10/36 c-kit+ CD34+ samples expressing CD56 and 16/36 c-kit+ CD34+ samples being CD7 positive; two c-kit+ CD34+ specimens carried the B-cell antigen CD19. In correlation to clinical outcome c-kit expression as single parameter was not predictive for poor response to therapy and short survival as previously suggested.

Aged↗
PubMed1994

[The extravascular contractile system of the human placenta: a new aspect for function of the organ?].

In the chorionic plate and stem villi of the human placenta besides the fetal blood vessel system a second extravascular contractile system (EVCS) exists. The cells of this system contain contractile and intermediate filaments and are dipeptidyl peptidase-IV- and NO-synthase-type-I-(NOS)-immunoreactive. Therefore it can be assumed that these cells cleave the vasodilator Substance P (by DPP IV) and produce NO (by NOS) and may contribute to a modulation of the EVCS.

Amino Acid Oxidoreductases↗
PubMed1994

[The lidocaine test in tinnitus. Determination of its current status].

Intravenous administration of high doses of lidocaine has been used as a treatment modality for tinnitus. From 1991 to 1992 we treated 108 patients with high-dose lidocaine and had each patient complete a special tinnitus questionnaire. The effects of therapy were estimated on patients' subjective responses concerning loudness, suppression, stress relationships and mastering of tinnitus. These parameters were recorded before and after 5 days of lidocaine therapy. Quantification of tinnitus in acute and chronic disease showed significant temporary diminution of tinnitus in all patients. Complete alleviation of tinnitus was so impressive that personal attitudes concerning tinnitus were changed. These findings demonstrated that lidocaine was a useful strategy for significant relief of symptoms due to tinnitus.

Administration, Oral↗
PubMed1994

Long-term sedation with propofol and green discolouration of the liver.

Propofol has been reported to cause discolouration of urine and hair. A case of green discolouration of the liver is reported in a 56-year-old man after long-term sedation with propofol in the intensive care unit. After discontinuation of propofol the discolouration of the liver disappeared. This phenomenon is due to metabolism of propofol which may lead to a phenolic green chromophore which is conjugated in the liver and excreted in the urine.

Chemical and Drug Induced Liver Injury↗
PubMed1994

Porphyrinogenic effects of atracurium, vecuronium, and pancuronium in a primed rat model.

Steroidal muscle relaxants might theoretically be contraindicated in acute hepatic porphyrias. Atracurium, on the other hand, has been proposed as the muscle relaxant of choice because of its extrahepatic degradation. To further investigate this problem, equipotent doses of atracurium, vecuronium, and pancuronium were determined in male Sprague Dawley rats, using evoked electromyography. After this pilot study, 64 rats were anesthetized, mechanically ventilated, and randomly allocated to eight groups. Animals in groups 1 through 4 received an intraperitoneal injection of arachis-oil 20 h before the experiments. For groups 5 through 8, an experimental porphyria was induced by use of the chemical substance 3,5-dicarbethoxy-1,4-dihydrocollidine (DDC), which was dissolved in arachis-oil and given 20 h prior to the beginning of the study. Rats of groups 1 and 5 served as controls; they received saline and were not given muscle relaxants throughout the experiment. For groups 2 and 6, atracurium was administered at a dosage of 4 mg/kg of body weight, followed by a continuous infusion of 15 mg/kg/h. Animals of groups 3 and 7 received vecuronium at a dosage of 1.5 mg/kg, followed by 7.5 mg/kg/h. For groups 4 and 8, pancuronium was given (0.75 mg/kg and 2.5 mg/kg/h, respectively). At the end of the 3-h study period, the liver was perfused and excised, and urine was obtained. Activity of the hepatic enzyme delta-aminolevulinic acid synthase (ALAS) and urinary concentrations of delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Aminolevulinate Synthetase↗
PubMed1994

Helicobacter pylori infection and serum pepsinogen A, pepsinogen C, and gastrin in gastritis and peptic ulcer: significance of inflammation and effect of bacterial eradication.

OBJECTIVES: To study the relationship between Helicobacter pylori infection, gastric inflammatory scores, and fasting gastrin and pepsinogen A and C concentrations, and to evaluate the effect of treatment on these parameters. METHODS: Gastrin and pepsinogen A and C concentrations were measured in 36 patients with gastritis, 10 gastric ulcer patients, 12 duodenal ulcer patients, and in 15 subjects with normal gastric mucosa, by standard radioimmunoassay techniques. Fifteen patients with H. pylori infection underwent triple therapy (bismuth subsalicylate, amoxicillin, metronidazole) and were reassessed 1 month later. RESULTS: Fasting gastrin and pepsinogen A and C concentrations were significantly higher in H. pylori-positive gastritis and peptic ulcer patients than in subjects with normal mucosa and in patients with H. pylori-negative gastritis. There was a significant correlation between inflammatory scores and serum gastrin (r = 0.45, p < 0.0001), and pepsinogen A (r = 0.33, p < 0.006) and pepsinogen C (r = 0.55, p < 0.0001) concentrations. Neither sex nor age affected basal gastrin and pepsinogen concentrations. Eradication of H. pylori infection was successful in 12 patients and resulted in a significant fall in serum gastrin and in pepsinogen A and C concentrations, and in a concomitant improvement of the inflammatory scores. Serum peptide levels and gastritis scores were unchanged in those patients in whom H. pylori infection persisted. CONCLUSIONS: These findings suggest that hypergastrinemia and hyperpepsinogenemia are secondary to H. pylori infection and are related to mucosal inflammation.

Amoxicillin↗
PubMed1994

[Hypercholesterolemia ].

This review article describes the types, pathophysiology, differential diagnosis and therapy of hypercholesterolemia. Special attention has been directed towards familiar hypercholesterolemia and familiar apolipoprotein B 100 defect. Clinically, both forms present very similar and may cause severe coronary arteriosclerosis and death before the age of 40 years. In the homozygote form CHD even develops prior to adolescence. With a frequency of 1:500 these forms of hypercholesterolemia are among the most common genetic disorders worldwide. The poor prognosis and their monogenetic dominant character emphasize the need for an exact distinction from the poligenetic forms of hypercholesterolemia and moreover underscore the necessity to screen for affected members in the family of already diagnosed cases and call for more aggressive therapeutic interventions. By dietary measures and monotherapy only 25% of patients reach the recommended cholesterol values. HMG-CoA reductase inhibitors proved to be the most effective. The remainders have to be treated with combinations of up to 3 lipid-lowering drugs. Alternative treatment such as extracorporal cholesterol elimination may become necessary.

Adolescent↗
PubMed1993

The fission yeast rad22 gene, having a function in mating-type switching and repair of DNA damages, encodes a protein homolog to Rad52 of Saccharomyces cerevisiae.

The gene rad22 of the fission yeast Schizosaccharomyces pombe has a function in DNA repair and mating-type switching. We have cloned the rad22 gene from a genomic gene bank by functional complementation of the switching defect. An open reading frame coding for a putative protein of 469 amino acids was found by sequence analyses. The rad22 gene contains no intron. A region of 126 amino acids in the N-terminal half of the Rad22 protein has significant homologies (56% identity and 36% similarity) to the Rad52 protein of Saccharomyces cerevisiae. A rad22 disruption strain was constructed which seems to be inviable in a homothallic background. Southern blot analyses have shown that the rad22-67 mutant frequently gives rise to deletions in the mating-type region. These data indicate that the Rad22 protein has a function in the repair of DNA double-strand breaks.

Amino Acid Sequence↗
PubMed1993

Identification of a chicken RAD52 homologue suggests conservation of the RAD52 recombination pathway throughout the evolution of higher eukaryotes.

Degenerate oligonucleotides encoding conserved regions of the Rad52 protein of S. cerevisiae and its homologue, the Rad22 protein of S. pombe, were used to clone a chicken RAD52 counterpart by the polymerase chain reaction. Sequence comparison of the chicken and yeast proteins reveals a strongly conserved region between positions 40 and 178 of the chicken Rad52 sequence indicating that this part of the protein is under strong evolutionary pressure. The first 39 amino acids and the 3' end of the chicken Rad52 homologue does not share significant similarity with the yeast proteins. High abundance of the mRNA in testis makes it likely that the chicken Rad52 protein plays a role in meiotic recombination.

Amino Acid Sequence↗
PubMed1993

Purine nucleotide levels in host tissues of Ehrlich ascites tumor-bearing mice in different growth phases of the tumor.

The pool sizes of purine nucleotides, nucleosides, and nucleobases were measured in the host tissues liver, skeletal muscle, and blood of Ehrlich ascites tumor-bearing mice during the different periods of tumor growth. There were large differences of tissue concentrations of these metabolites between control animals, animals in the logarithmic growth period of the Ehrlich ascites tumor, and animals in the resting phase of tumor growth. The ATP concentrations in liver, muscle, and erythrocytes were higher during the proliferating phase of the tumor compared with the ATP levels of these organs in healthy animals. In liver and skeletal muscle the ATP concentration decreased during the transition from proliferating into resting phase of tumor growth. The concentrations of nucleosides and nucleobases within the RBC and blood plasma deceased during the logarithmic growth phase but restored during the plateau period. As well as in the organs/cells investigated and in the body fluids (plasma, ascites fluid) a tremendous increase of adenosine concentration during the resting phase of tumor growth was observed. From changes of total purine ribonucleotide pattern an activation period in the nucleotide metabolic pathways of liver and skeletal muscle during the proliferating phase of tumor growth is postulated.

Adenine↗
PubMed1993

A ferro-heme protein senses oxygen levels, which modulate the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures.

Oxygen modulates the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK) gene. The respiratory chain or heme proteins have been proposed to function as O2-sensors. The functions of the respiratory chain are impaired by uncouplers such as 2,4-dinitrophenol (DNP); those of ferro-heme proteins are affected by carbon monoxide (CO), which locks heme in the oxy conformation. Therefore, the effects of different concentrations of CO and DNP on the glucagon-dependent induction of PCK mRNA and PCK activity were investigated at different physiological oxygen tensions in primary rat hepatocyte cultures. The cells were cultured under standard conditions from 4-24 h. After addition of fresh media PCK was induced with 1 nM glucagon. PCK mRNA and PCK activity were elevated after 2h and 3h, respectively, to 100% at 16% O2 (mimicking arterial oxygen tensions) and to about 60% at 8% O2 (mimicking venous oxygen tensions). CO counteracted the reduced induction at lower oxygen tensions: Under 8% O2 + 2% CO PCK mRNA could be elevated again to about 90% and PCK activity to about 80%. CO did not impair the induction by insulin of ornithine decarboxylase (ODC) and the incorporation of 14C-leucine into total protein. CO did not cause lactate dehydrogenase (LDH) to leak from the cells or influence the cell structures at the microscopical level. DNP (50 microM) unspecifically lowered PCK gene expression without affecting its modulation by oxygen. These results are in line with the proposal that a ferro-heme protein rather than the respiratory chain acted as an O2 sensor in the activation of the PCK gene.

Animals↗
PubMed1993

Exendin-4 is a high potency agonist and truncated exendin-(9-39)-amide an antagonist at the glucagon-like peptide 1-(7-36)-amide receptor of insulin-secreting beta-cells.

Exendin-4 purified from Heloderma suspectum venom shows structural relationship to the important incretin hormone glucagon-like peptide 1-(7-36)-amide (GLP-1). We demonstrate that exendin-4 and truncated exendin-(9-39)-amide specifically interact with the GLP-1 receptor on insulinoma-derived cells and on lung membranes. Exendin-4 displaced 125I-GLP-1, and unlabeled GLP-1 displaced 125I-exendin-4 from the binding site at rat insulinoma-derived RINm5F cells. Exendin-4 had, like GLP-1, a pronounced effect on intracellular cAMP generation, which was reduced by exendin-(9-39)-amide. When combined, GLP-1 and exendin-4 showed additive action on cAMP. They each competed with the radio-labeled version of the other peptide in cross-linking experiments. The apparent molecular mass of the respective ligand-binding protein complex was 63,000 Da. Exendin-(9-39)-amide abolished the cross-linking of both peptides. Exendin-4, like GLP-1, stimulated dose dependently the glucose-induced insulin secretion in isolated rat islets, and, in mouse insulinoma beta TC-1 cells, both peptides stimulated the proinsulin gene expression at the level of transcription. Exendin-(9-39)-amide reduced these effects. In conclusion, exendin-4 is an agonist and exendin-(9-39)-amide is a specific GLP-1 receptor antagonist.

Animals↗
PubMed1993

Lymphocytopenia as an unfavorable prognostic factor in patients with cytomegalovirus infection after bone marrow transplantation.

Sixty-three recipients of an allogeneic marrow transplant were screened for the occurrence of cytomegalovirus (CMV) infection and clinical parameters possibly predicting the development of CMV disease in a retrospective study. Blood and urine samples obtained from these patients were screened weekly after bone marrow transplantation (BMT) for the presence of CMV by polymerase chain reaction (PCR) and virus culture technique. Forty-six of the 63 patients studied were found to be CMV-positive by PCR technique in blood and urine samples at a median of 29 days after BMT. In 33 of these 46 patients, CMV could be cultured from urine samples and 16 of the 46 had culture-positive viremia. Twenty-eight of these 46 PCR-positive patients developed CMV disease. Whereas PCR assays showed an optimal negative predictive value and sensitivity for the development of CMV disease, their positive predictive value was 61% and could not be remarkably increased when culture-proven viruria (64%) and viremia (69%) were considered. Acute graft-versus-host disease (GVHD) grade 2 to 4 (P < .05), but not underlying disease, conditioning therapy, or GVHD prophylaxis, was associated with CMV infection. On day +49, a remarkable decrease (P < .001) in the lymphocyte count, as well as in the absolute number of CD4+, CD8+, and CD56+ lymphocytes, occurred only among the patients who later developed CMV disease. The decrease of all of these cell counts, but predominantly the CD4+ T cells, to less than 100/microL on day +49 after BMT showed a very high positive predictive value (100%) for the development of CMV disease in patients with PCR-proven viremia. Persisting CD4 lymphopenia after antiviral therapy was only observed in patients who finally died of CMV disease. Thus, immunophenotyping of the patients after BMT in addition to a highly sensitive virus detection assay might help to identify patients at high risk to develop CMV disease and indicate the need for additional adoptive immunotherapy.

Adolescent↗
PubMed1993

The fission yeast prp4+ gene involved in pre-mRNA splicing codes for a predicted serine/threonine kinase and is essential for growth.

Only four prp (pre-mRNA processing) genes of the fission yeast Schizosaccharomyces pombe have been reported. We exploited yeast genetics and identified and isolated the prp4 gene. Sequence analysis revealed that the splicing factor encoded by this gene contains the signature sequences that define the serine/threonine protein kinase family. This is the first kinase gene identified whose product is involved in pre-mRNA splicing. The prp4 gene contains one intron in the kinase domain. Gene replacement studies provided evidence that this gene is essential for growth and is located on chromosome III.

Amino Acid Sequence↗
PubMed1993

Genotype-phenotype correlations in phenylketonuria.

Genotyping of the phenylalanine hydroxylating system offers a new way of characterizing patients with phenylalanine hydroxylase (PAH) deficiency. This paper investigates the power of genotyping as a parameter for differential diagnosis and as a measure of the risk factor of brain damage in well-treated patients with phenylketonuria (PKU). Thirty-three PKU patients were followed up over 9 years and the quality of dietary treatment, plasma phenylalanine (phe) in the newborn period before treatment and intellectual outcome at the age of 9 years were measured and correlated with the predicted residual activity (PRA) of the phe hydroxylase system as estimated from mutation analysis of the PAH gene. Patients were grouped in group Ia (PRA = 0%), group Ib (PRA = 5-15%) and group II (PRA > or = 25% of the normal activity). Mean plasma phe levels in the newborn in group Ia were 37.9 +/- 6.5 (2296 +/- 394), in group Ib 40.8 +/- 15.9 (2472 +/- 963) and in group II 16.2 +/- 4.2 (981 +/- 254) mg/dl (mumol/l). Difference in mean plasma values of groups Ia and Ib on the one hand and group II on the other were highly significant (P < 0.0001). No difference could be seen between groups Ia and Ib. There was a higher mean IQ at the age of 9 years in group II (97.4 +/- 5.4) in comparison with groups Ia (92.7 +/- 12.8) and Ib (85.0 +/- 14.4). The difference between group Ib and group II was significant (P < 0.040).(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1993

Optimized separation of purine bases and nucleosides in human cord plasma by capillary zone electrophoresis.

An optimized separation of the main purine compounds of human serum by capillary zone electrophoresis is presented. Separations were performed in an uncoated silica capillary (44 cm x 75 microns I.D., 37 cm to window) on a SpectraPhoresis 1000 system with UV detection. The separation of adenine (Ade), adenosine (Ado), guanine (Gua), guanosine (Guo), hypoxanthine (Hyp), inosine (Ino), xanthine (Xan) and uric acid (UA) was optimized with respect to pH, temperature, applied potential and hydrodynamic injection time. Optimum conditions were 20 mM borate buffer (pH 9.4), 37 degrees C, 20 kV and 9 s load and detection at 260 nm. Linearity extended from 1 to 125 microM. The sensitivity of the method was 0.5 microM, which is adequate for measuring Ade, Gua, Hyp and UA in plasma samples. Plasma samples from newborns were precipitated with an equal volume of perchloric acid (7%, v/v), the supernatant was adjusted to neutral pH with potassium carbonate and, before injection, the sample was alkalized with sodium hydroxide. The method presented here allows the determination of Ade, Guo, Hyp and UA. The levels of the determined purines were compared in samples from control newborns, preterm babies and newborns with asphyxia or acidic serum pH values.

Calibration↗